Adeno-associated viruses (AAV) are non-enveloped, non-pathogenic viruses with a single-stranded genome approximately 4.7 kb in length of either positive or negative polarity. The replication of AAV necessitates a coinfection with helper virus such as Adenovirus or Herpes Simplex virus. In the absence of helper virus, AAV integrates into the host chromosome to establish a latent infection. AAV has been isolated from many organisms including human, nonhuman primates, ovine, avian, snake, bovine, murine, and caprine (1-13). It has been reported that various AAV serotypes have differing tropisms and can transduce specific organs more efficiently than others, such as the high transduction efficiency of AAV5 in airway epithelial, muscle, and retina cells as compared to AAV2 (14, 15).
Gene transfer vectors derived from AAV can deliver genes in a variety of tissues in vivo. Recent observations have also promoted the evaluation of AAV as potential genetic vaccine vectors due to their long-term expression profile which can stimulate robust antibody responses (16, 17). Currently, clinical trials are taking place using AAV as a vector for the treatment of ailments such as Parkinson's disease, Cystic fibrosis, Leber's congenital amaurosis, HIV infection, and various other genetic disorders (18, 19, 20, 21). These recombinant AAV (rAAV) vectors are based on the well characterized human AAV serotype 2 which is seroprevalent in up to 80% of the human population with neutralising antibodies found in 35% of them (22).
The AAV capsid proteins encoded by the cap gene were shown to be the main determinant for tissue tropism and constitute an important target for the immune response. The cap gene encodes three proteins expressed from two different alternatively spliced transcripts; VP1, VP2, and VP3. Some serotypes of AAV were found to be less immunogenic than others which may translate into better gene transfer vehicle and less efficient vaccine vector or vice versa (23, 24, 25). In the past, AAV has conventionally been isolated from contaminated adenoviral stocks or young, sick animals or children (1, 2, 3, 4, 5, 6, 7, 9, 12). Recently, isolation of new AAV isolates was extensively performed using PCR amplification of AAV sequences from genomic DNA of different animal species (8, 10, 11, 13). In this study, novel porcine AAV sequences were identified by PCR using genome walking strategies. We describe the isolation of novel AAVpo1 and the characterisation of the serological profile and tissue tropism in vitro and in vivo.
Adeno-associated virus (AAV) is a non-pathogenic parvovirus with a single-stranded DNA genome. The virus typically has a relatively small genome size.
While other parvoviruses replicate autonomously, wild type AAV requires co-infection with a helper virus for lytic phase reproduction. In the absence of a helper virus, wild-type AAV establishes a latent, non-productive infection with long-term persistence.